Cardiac hypertrophy is a compensatory mechanism triggered by increased systolic wall stress. If the initiating stimulus is not corrected, the heart often undergoes a transition to congestive heart failure. The pathophysiologic mechanisms still remain unclear despite intense investigation. Recently, the transcriptional co-activator beta-catenin has been implicated in the development of cardiac hypertrophy. Elevated beta-catenin levels occur in response to hypertrophic stimuli and have been associated with cardiac hypertrophy in vivo. Our research objective is to determine the role of beta-catenin in the development of cardiac hypertrophy. The 3 specific aims of the proposal are the following: 1) Determine if beta-catenin is sufficient to evoke hypertrophic responses in cardiomyocytes in culture. For these studies, neonatal rat ventricular myocytes (NVRM) will be infected with an adenovirus encoding stable B-catenin to determine if beta-catenin is sufficient to induce cardiac hypertrophy. 2) Determine if beta-catenin is necessary for the development of cardiomyocyte hypertrophy in cells in culture. NRVMs will be infected with an adenovirus expressing a dominant inhibitory mutant of beta-catenin?s partner, the transcription factor Tcf/Lef-1, to determine whether expression of this mutant blocks the hypertrophic response. 3. Determine if beta-catenin is sufficient to evoke cardiomyocyte hypertrophy in vivo. Gene transfer of stabilized beta-catenin in adult rat hearts will be used to determine whether this alone is sufficient to induce hypertrophic responses in vivo.